Changes in thymopoiesis in myasthenia gravis

Abstract

This study was undertaken to investigate T-cell maturation ill hyperplastic thymi of patients suffering from myasthenia gravis (MG). For this purpose, the expression of the major differentiational molecules (CD4, CD8, and CD3/TCRalphass) and that of the regulator. v and activation molecules oil thymocytes from MG patients and control subjects were estimated by flow cytometric analysis. In the MG patients the increase in relative proportion of immature (CD4-8- TCRalphass-) and the most mature (CD4+8- TCRalphass(high) and CD4-8- TCRhigh encompassing immunoregulatory NKT) thymocytes followed by a decrease in that of CD4+8+CD3 /TCRalphass- cells was found. Furthermore, in these patients the relative proportion of CD4+HLA-DR+ and CD4+71+ cells was increased, whereas that of CD4+25+ cells was slightly, but significantly, decreased (reflecting, most likely, decreased contribution of T reg cells bearing this phenotype). Moreover. in MG thymi the percentage of CD45RA+ cells was reduced indicating changes in the selection processes. In keeping with this finding the reduced thymocyte apoptotic index and percentage of cells bearing apoptosing (CD4-8- TCRalphass(low)) phenotype were detected. In conclusion, the study demonstrates substantial changes in intrathymic differentiation of T cells in hyperplastic MG thymi and suggests alterations in selection events providing an increased escape of potentially? autoreactive T-cell clones, on one side, and all altered maturation and/or selection of immunoregulatory cells (NKT and CD4+8-25+ T reg cells) keeping these cell clones under control, on the other side.